Post-transcriptional regulation of transferrin receptor mRNA levels by iron is mediated by a portion of the 3' untranslated region (UTR) of the mRNA. We have previously shown that a 678 nucleotide fragment of the 3' UTR contains the regulatory element(s). Within this region are five RNA structures which resemble the iron responsive element (IRE) in the 5' untranslated region of the ferritin mRNA, which is regulated translationally by iron. The IRE's from the ferritin and transferrin receptor mRNA's compete in an in vitro assay for interaction with a cytoplasmic protein; the activity of this IRE-binding protein is dependent upon the iron status of the cells. Thus, despite the differences in the translational regulation of ferritin and the regulation of TfR mRNA levels, these two post-transcriptional regulatory mechanisms share a cis-acting RNA element (IRE) and a transacting cytoplasmic protein that interacts with the two mRNA's. We are attempting to understand more fully the mechanism of the regulation of TfR expression.